Evidence map›Paper›PMID 36357719›Full record

ArticleNature biotechnology2023

Evolution of an adenine base editor into a small, efficient cytosine base editor with low off-target activity.

Monica E Neugebauer, Alvin Hsu, Mandana Arbab, Nicholas A Krasnow, Amber N McElroy, Smriti Pandey, Jordan L Doman, Tony P Huang, Aditya Raguram, Samagya Banskota and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Nature biotechnology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers.

0numbers the graph read from it
0cells of the map it votes in
182citing papers in PubMed
21.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

182 citing papers in PubMed, 252 citations in OpenAlex.

  1. Article
  2. Base Editing: Mechanisms and Therapeutic Applications.Methods in molecular biology (Clifton, N.J.) · 2027
    Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Engineered Transformer Base Editor with Enhanced Editing Efficiency.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
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  18. Article
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  20. Article

122 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 1 country.

Monica E NeugebauerMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Alvin HsuMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-4034-2788
Mandana ArbabMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nicholas A KrasnowMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-4131-1855
Amber N McElroyDepartment of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA.ORCID http://orcid.org/0000-0002-4169-0015
Smriti PandeyMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jordan L DomanMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Tony P HuangMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2904-830X
Aditya RaguramMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Samagya BanskotaMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Gregory A NewbyMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-7869-2615
Jakub TolarDepartment of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA.
Mark J OsbornDepartment of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA.
David R LiuMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA. drliu@fas.harvard.edu.ORCID http://orcid.org/0000-0002-9943-7557
Broad Institute · USUniversity of Minnesota Medical Center · US

Funding

Trial Design and Biostatistical Support CoreP01CA065493 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Mark J Osborn · 1995 to 2026
$48.2M
Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human DiseaseRM1HG009490 · NHGRI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI Brittany S. Adamson, Martin Joseph Ankrah Aryee · 2017 to 2026
$22.7M
Stem Cell and Transplantation BiologyU54DK106829 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI DEREK L STIREWALT · 2015 to 2026
$9.1M
Integrating Chemistry and Evolution to Illuminate Biology and Enable Novel TherapeuticsR35GM118062 · NIGMS · HARVARD UNIVERSITY · PI LIU, DAVID R · 2016 to 2025
$6.4M
ePACE: automation platforms for adaptable and scalable continuous evolution of biomolecules with therapeutic potentialR01EB027793 · NIBIB · BROAD INSTITUTE, INC. · PI Ahmad Samir Khalil, DAVID R LIU · 2019 to 2026
$6.1M
Skin-targeted Cell Therapy for Recessive Dystrophic Epidermolysis BullosaR01AR063070 · NIAMS · UNIVERSITY OF MINNESOTA · PI Mark J Osborn, Jakub Tolar · 2013 to 2026
$4.5M
Continuous Evolution of Proteins with Novel Therapeutic PotentialR01EB031172 · NIBIB · BROAD INSTITUTE, INC. · PI LIU, DAVID R · 2021 to 2024
$2.5M
Expanding the Scope of Base EditingU01AI142756 · NIAID · BROAD INSTITUTE, INC. · PI LIU, DAVID R · 2018 to 2022
$2.1M
Precision Base Editing for the Treatment of Motor Neuron DiseasesK99NS119743 · NINDS · BROAD INSTITUTE, INC. · PI ARBAB, MANDANA · 2021 to 2022
$253k
Directed Evolution of an Epitranscriptomic ToolkitF32GM143776 · NIGMS · BROAD INSTITUTE, INC. · PI NEUGEBAUER, MONICA · 2021 to 2023
$205k
Howard Hughes Medical InstituteNCI NIH HHS P01 CA065493NHGRI NIH HHS RM1 HG009490NIAID NIH HHS U01 AI142756NIAMS NIH HHS R01 AR063070NIBIB NIH HHS R01 EB027793NIBIB NIH HHS R01 EB031172NIDDK NIH HHS U54 DK106829NIGMS NIH HHS F32 GM143776NIGMS NIH HHS R35 GM118062NINDS NIH HHS K99 NS119743
6 · The paper itself

Abstract

Cytosine base editors (CBEs) are larger and can suffer from higher off-target activity or lower on-target editing efficiency than current adenine base editors (ABEs). To develop a CBE that retains the small size, low off-target activity and high on-target activity of current ABEs, we evolved the highly active deoxyadenosine deaminase TadA-8e to perform cytidine deamination using phage-assisted continuous evolution. Evolved TadA cytidine deaminases contain mutations at DNA-binding residues that alter enzyme selectivity to strongly favor deoxycytidine over deoxyadenosine deamination. Compared to commonly used CBEs, TadA-derived cytosine base editors (TadCBEs) offer similar or higher on-target activity, smaller size and substantially lower Cas-independent DNA and RNA off-target editing activity. We also identified a TadA dual base editor (TadDE) that performs equally efficient cytosine and adenine base editing. TadCBEs support single or multiplexed base editing at therapeutically relevant genomic loci in primary human T cells and primary human hematopoietic stem and progenitor cells. TadCBEs expand the utility of CBEs for precision gene editing.

Indexed as

CRISPR-Cas SystemsCytosineAdenineCytidineDeoxyadenosinesDNAGene EditingHumansAdenineCytidineCytosineDeoxyadenosinesDNA

Identifiers

PMID36357719
PMCPMC10188366
OpenAlexW4308772150

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.